Abstract
Photodynamic therapy of superficial basal cell carcinoma using topical 5-aminolevulinic acid and a light fluence of 75-100 J cm−2 yields unsatisfactory long term clinical response rates. In a range of pre-clinical models illumination with two light fractions separated by 2 hours apart was considerably more effective than single illumination. Response is further enhanced if the fluence of the first light fraction is reduced while the cumulative fluence is maintained. We have demonstrated that these encouraging pre-clinical results are also evident for the clinical ALA-PDT of the treatment of superficial basal cell carcinoma. In a large scale randomised study including 505 primary sBCC we have shown that therapy using two light fractions of 20 and 80 Jcm−2 performed 4 and 6 hours after the application of a single dose of 20% ALA results in a significant increase in complete response (P ̃ 0.002, log-rank test). Twelve months after therapy, complete response rate following a two-fold illumination is 97% whereas the complete response to a single illumination is 89%. Numerous studies are underway investigating the mechanism underlying the increase in tissue response. Increased efficacy is not simply associated with an increasing PpIX content of the tissues during the treatment scheme and there is no direct relationship between the total amount of PpIX utilised and efficacy. We have shown that fractionated illumination does not enhance the efficacy of PDT using methyl-ester derivatives of ALA despite almost identical PpIX fluorescence kinetics during therapy. Our most recent data suggest that the in-vivo distribution of MAL and ALA and the exact site of PDT induced damage, is an important parameter in the mechanism underlying fractionated illumination for ALA-PDT. There is significant potential for the future use of light fractionation in other organs.
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Robinson, D., Bruijn, H.d., Haas, E.d., Neumann, H., Sterenborg, H. (2008). Light Fractionated ALA-PDT: From Pre-Clinical Models to Clinical Practice. In: Waynant, R., Tata, D.B. (eds) Proceedings of Light-Activated Tissue Regeneration and Therapy Conference. Lecture Notes in Electrical Engineering, vol 12. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-71809-5_10
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DOI: https://doi.org/10.1007/978-0-387-71809-5_10
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